CYLC2 p.Glu65=
c.195A>G · VCV3837732
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.1%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.66 | GERP -3.6 |
| Overall | ||
| CADD | 0.246 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.1%
Middle Eastern · 6/5,998 alleles
Filtering AF
0.0435%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0297%
Overall
0.00396%
63/1,590,360 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.1% | 1,000 |
| South Asian | 0.0104% | 9,621 |
| Remaining individualsnot grpmax-eligible | 0.00974% | 10,264 |
| European (non-Finnish) | 0.0035% | 28,593 |
| African / African-American | 0.00136% | 73,446 |
Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.
Variant & gene context
- Gene
- CYLC2
- Protein
- p.Glu65=
- Coding
- c.195A>G
- MANE Select
- NM_001340
- Type
- single nucleotide variant
- Location
- chr9:103004709 (GRCh38)
- Gene constraint
- LOEUF 1.608 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 50.39
- Residue 65
- the '31 x 3 aa repeats of k-k-x' region
Similar variants
- CYLC2 p.Asp330His Uncertain significance ★★ ⚠ same type
- CYLC2 p.Ala175Val Uncertain significance ★ ⚠ same type
- CYLC2 p.Ala296Thr Uncertain significance ★ ⚠ same type
- CYLC2 p.Ala327Glu Uncertain significance ★ ⚠ same type
- CYLC2 p.Arg42Gln Uncertain significance ★ ⚠ same type
- CYLC2 p.Arg55Gln Uncertain significance ★ ⚠ same type
- CYLC2 p.Arg55Trp Uncertain significance ★ ⚠ same type
- CYLC2 p.Arg71Gly Uncertain significance ★ ⚠ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cylc2-p-glu65 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown